Revised Category II regimen as an alternative strategy for retreatment of Category I regimen failure and irregular treatment cases.

Currently, the Category (CAT) II regimen is recommended for patients who have failed the CAT I regimen. We have determined before that prevalence of multidrug-resistant tuberculosis (MDR TB) is relatively high among these patients. On the other hand, the retreatment success rate with CAT II in CAT I treatment failures and defaults is nearly 50%. Therefore, we tried to find another strategy with a higher success rate. From January 2004 to November 2007, 105 patients with pulmonary TB, who failed a prior CAT I regimen or with more than one course of irregular anti-TB treatment, were included in this study, whereas five cases with nontuberculous mycobacteria were excluded. Drug susceptibility testing (DST), for first line anti-TB drugs, and polymerase chain reaction were performed. By the time of availability of DST that took 3 to 4 months, a pilot protocol consisted of isoniazid, rifampin, ethambutol, ofloxacin, cycloserine, and amikacin was started. Then therapeutic regimen was adjusted based on four categories of DST pattern: sensitive, non-MDR pattern, MDR pattern, and culture-negative. Sensitive patients received the standard CAT I regimen, non-MDR patients an individualized regimen based on DST, MDR patients a standard second-line regimen, and culture-negatives a standard CAT I plus a 6-month injectable agent. Treatment outcomes were categorized and analyzed. Forty-eight patients with prior CAT I treatment failure and 52 with more than one irregular treatment courses were included in the analysis. Six percent of subjects had confirmed HIV infection. Seventy-two percent of subjects were assigned to a good outcome and 28% were assigned to a poor outcome group. Seventeen percent were culture-negative. Regarding DST pattern, 13% isolated strains were completely sensitive to first-line drugs. 53% strains were MDR, 10% monodrug-resistant, and 7% polydrug-resistant. There was no significant association between DST pattern and outcome (P = 0.13). The irregular regimen was associated with MDR TB as twice as CAT I regimen failure (69.2% versus 35.4%, P = 0.004). Patients with MDR TB significantly experienced more side effects than non-MDR-TBs (47% versus 27%, P = 0.102). Of 100 patients, 72% were cured, 5% abandoned treatment, 12% died, 6% were classified as treatment failures, 1% relapsed, and 5% were transferred out. Of 53 patients with MDR TB, 33 subjects were cured and seven died. All together, successful outcome was achieved in 62.2%, 76%, and 76% of MDR TB, non-MDR TB, and completely sensitive cases, respectively. A retreatment strategy based on DST and replacing the Category II regimen with an intermediate regimen called revised CAT II may improve clinical outcomes among Category I treatment failures and defaults who found to have active, infectious MDR TB. This strategy significantly reduces delays to MDR TB diagnosis and to the initiation of MDR TB therapy. Success rate of this strategy is 62.2% and 72% in MDR TB and overall CAT I failure cases and defaulters, respectively.

Impact of extensively drug-resistant tuberculosis on treatment outcome of multidrug-resistant tuberculosis patients with standardized regimen: report from Iran.

The limited experience in treating patients with extensively drug-resistant tuberculosis (XDR-TB) shows a therapeutic success rate under 50-60% and there are no publications regarding the outcome of these patients treated with standardized regimens. All multidrug-resistant tuberculosis (MDR-TB) patients hospitalized at the Masih Daneshvari Hospital in Tehran, Iran, during 2004-2007 were recruited. Drug susceptibility testing to 14 drugs (including eight second-line drugs) was performed and a standardized regimen with ofloxacin, cycloserine, prothionamide, and amikacin was administered for all patients. Outcome of the patients was studied, comparing between the MDR-TB non-XDR-TB and the XDR-TB. Fifty-one patients were included, 12 with XDR-TB criteria. Of 51, 48 were HIV negative and HIV status was unknown in three cases. All 12 were HIV negative. XDR-TB infection was significantly associated only with age (p = 0.039). The success rates for the total 51 MDR-TB, the 39 MDR-TB non-XDR-TB, and the 12 XDR-TB patients were 76.5% (39 patients), 87.2% (34 patients), and 41.7% (5 patients), respectively. Resistance to ofloxacin, ciprofloxacin, and amikacin were found to be significantly associated with unsuccessful outcome. In this setting, a standardized second-line drugs regimen produces high treatment success rates in MDR-TB patients unless XDR-TB is present.

Extensively drug-resistant tuberculosis treatment outcome in Iran: a case series of seven patients.

BACKGROUND: Extensively drug-resistant tuberculosis (XDR-TB) has recently been identified as a major threat to global health. XDR-TB poses a risk of higher failure rates and death during TB treatment. We report herein the outcomes of XDR-TB in patients treated with the standardized regimen in Iran. PATIENTS AND METHODS: Between 2002 and 2006, seven patients were diagnosed with XDR-TB. All patients were treated with the standardized second-line regimen containing cycloserine, prothionamide, amikacin, and ofloxacin. First-line drugs, such as ethambutol and pyrazinamide, were added to the regimen if drug susceptibility testing showed sensitivity to these drugs. RESULTS: Four (57.1%) patients were male. All seven patients were HIV-negative. The patient age range was 22-79 years. Of the seven cases, the final outcome was 'cure' in two (28.6%), 'relapse' in one, 'treatment failure' in one, and 'death' in two; the outcome for one patient was unknown. CONCLUSION: Our study shows a poor prognosis in patients with XDR-TB. This indicates the necessity of detecting XDR-TB cases earlier, as well as the need to gain access to more second-line agents. This is particularly important in resource-limited settings in order to administer individualized regimens.

First-line anti-tuberculosis drug resistance patterns and trends at the national TB referral center in Iran--eight years of surveillance.

OBJECTIVE: Resistance to anti-tuberculosis (anti-TB) drugs is becoming a major and alarming threat in most regions worldwide. METHODS: This was a descriptive cross-sectional study at a tertiary hospital in Iran, using patient medical records for 2000-2003. The findings were analyzed following the same framework as that used for previous reports from this center. RESULTS: Among 1556 TB patients, drug susceptibility testing (DST) was performed for 548 culture-positive cases. Anti-TB drug resistance to both isoniazid and rifampin was identified in 10 (2.8%) of the new TB cases (multidrug-resistant TB; MDR-TB). Any resistance was detected in 228 (41.6%), showing an increasing trend in both new and retreatment cases. The data analysis revealed that drug-resistant TB had a statistically significant association with Afghan ethnicity, age>65 years, and the type of disease (retreatment vs. new TB case) (p<0.05). Also, assessment of the drug resistance trends showed a significant increase in resistance to any anti-TB agent, to isoniazid, and to streptomycin in new cases, and to all of the first-line anti-TB drugs in retreatment patients. CONCLUSIONS: There has been an increasing trend in drug resistance in recent years, particularly in retreatment cases. Hence, revision of the national TB control program, reevaluation of the role of the World Health Organization category II (CAT II) regimen, as well as the conducting of a nationwide drug resistance survey, are recommended.

Is standardized treatment appropriate for non-XDR multiple drug resistant tuberculosis cases? A clinical descriptive study.

The clinical relevance of second-line drug susceptibility test (DST) results with respect to treatment outcome is unknown in non-XDR MDR patients. This study was carried out in the sole national referral centre for TB in Iran between 2002 and 2006. Multidrug-resistant tuberculosis (MDR-TB) patients who had DST to second-line drugs were included. For all MDR-TB patients the standard second-line regimen was initiated. Outcome of treatment based on DST to second-line drugs was analysed. 53 patients were included. DST for second-line drugs was available for 40 patients. Seven patients returned to Afghanistan during treatment. Among the remainder, 13 (30.4%) cases were Iranian. Mean age was 40.8 + 19.7 y. The relatively small sample size imposes some limitations on this study. However, in this study, there was no difference in resistance to second-line drugs by nationality. No significant correlation was seen between resistance to second-line drugs and outcome of treatment. In conclusion, the treatment outcome according to WHO definitions was appropriate in the study population by the use of standardized treatment regimens. Follow-up studies on a long-term basis are however needed in order to detect possible relapses.

Representative drug susceptibility patterns for guiding design of re-treatment regimens for multidrug-resistant tuberculosis in Iran.

BACKGROUND AND OBJECTIVE: The prevalence of multidrug-resistant tuberculosis (MDR-TB) has increased substantially in the past 20 years, however, there are no data specific to Iran. This study investigated patients suspected to have MDR-TB, attending the TB referral hospital in Iran. METHODS: All patients suspected of having MDR-TB on hospital admission in the period 2003-2005 were included in this study. Sputum from all patients was tested for smear and culture, and drug sensitivity testing was performed using the proportion method. Patients were categorized into three groups based on their history of medical treatment. Group I consisted of patients with CAT I regimen failure; Group II consisted of patients with a history of CAT II regimen failure and Group III comprised patients with a history of more than two courses of irregular CAT I anti-TB regimen. RESULTS: There were 105 patients recruited; 32 in Group I, 53 in Group II and 20 in Group III. There were no significant differences between the three groups in their resistance to first-line anti-TB drugs. Fifty-five patients were diagnosed with MDR-TB. The prevalence of MDR-TB was 56% (18 cases) in group I, 49% (26 cases) in group II and 55% (11 cases) in group III. No significant difference in the pattern of drug resistance was observed between the three groups. CONCLUSION: The prevalence of MDR-TB was high in this study. The lack of response of MDR-TB patients to CAT II treatment indicates that antibiotic sensitivity testing is essential in patients with CAT I treatment failure.

Trends of drug resistant Mycobacterium tuberculosis in a tertiary tuberculosis center in Iran.

OBJECTIVE: To determine the drug resistance pattern to first line antituberculous drugs in National Research Institute of Tuberculosis and Lung Disease and to compare resistant rates with previous studies. METHODS: An anterograde cross-sectional study was performed. The study includes all adults with documented pulmonary tuberculosis (TB) that were hospitalized in National Research Institute of Tuberculosis and Lung Disease in Tehran, from June 2003 to September 2004. Demographic characteristic, TB categories, and drug susceptibility test results were recorded. Two previous studies regarding drug susceptibility in Iran were selected as historical controls. RESULTS: One hundred and ninety-six new cases and 68 previously treated patients were enrolled in the study. The strains of 61% of new patients and 21% of previously treated patients were fully sensitive to all drugs. The most common resistance was streptomycin (27%) followed by isoniazid (23%) in new cases. Multiple drug resistant strains were noted in 2.6% (95% CI 0.8% to 5.8%) of new cases versus 56% (95% CI 43% to 68%) in previously treated group. The frequency of primary drug resistance to isoniazid was 9.8%-15% or streptomycin 9.8%-13% in the previous studies (p<0.00001). CONCLUSION: While these rates may not reflect the true prevalence of drug resistance on a national scale, it does partially demonstrate some defects in the existing tuberculosis control program. The significant increase of isoniazid and streptomycin resistance in the last few years would present a serious challenge to effective management of TB.